This application relates to the treatment of squamous cell carcinomas using a combination of radiation and an agent that inhibits the level of heat shock protein 27 (hsp27) expression.
Squamous cell carcinoma is a cancer that begins in squamous cells—thin, flat cells that look under the microscope like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of hollow organs of the body, and the passages of the respiratory and digestive tracts. Squamous cell carcinomas may arise in any of these tissues. Thus, some skin cancer, head and neck cancer, lung cancer, mouth cancer, breast, esophageal cancer, and cervical cancer are cancers of squamous cell origin. Although it is rare, primary squamous cell cancer of the prostate may also occur. Treatment for squamous cell cancer may involve treatment with radiation with or without surgical removal of the tumor mass.
Hsp27 is a known inhibitor of apoptotic cell death in various types of cancers, including some squamous cell carcinomas and can act as a means for protecting cells against chemotherapy agents. Huot et al. (1991) Cancer Res. 51: 5245-5252; Oesterreich et al. (1993) The small heat shock protein hsp27 is correlated with growth and drug resistance in human breast cancer cell lines. Cancer Res. 53: 4443-4448; Garrido et al. (1997) Cancer Res. 57: 2661-2667; Yonekura et al., (2003) Cell Death and Differentiation 10, 313-322. On the other hand, it has been reported that there is no correlation between overexpression of hsp27 expression and resistance of squamous cell head and neck cancer to radiotherapy, even though there is a correlation between hsp27 over expression and heat and drug resistance. Fortin et al., (2000) Int. J. Radiation Oncology Biol. Phys. 46: 1259-1266.
U.S. Pat. No. 7,101,991, which is incorporated herein by reference, discloses oligonucleotide therapeutic agents that target hsp27. Reduction in hsp27 expression was shown to reduce progression of non-squamous prostatic tumor cells to androgen independence, and also to enhance to sensitivity of such prostate tumor cells to chemotherapy.